Gastrointestinal stromal tumor (GIST)

Gastrointestinal stromal tumors (GISTs) are among a group of cancers known as sarcomas. The number of new cases in the United States each year has been estimated at 5,000–6,000. These tumors arise from nerve cells in the wall of the gastrointestinal (GI) tract and can occur anywhere from the esophagus to the rectum. However, most arise in the stomach (55%) and the small intestine (29%), while the colon/rectum (3%) and esophagus (0.5%) are less common sites of the disease. There have also been rare reports of tumors arising in the appendix, pancreas, gallbladder, and lining of the abdominal cavity.

These tumors most commonly present with non-specific symptoms, including feeling full sooner than normal after eating (early satiety) and abdominal pain, but may also present with bleeding or signs of intestinal obstruction. They spread most commonly to sites within the abdominal cavity and to the liver, although certain subtypes spread to lymph nodes and very rare cases spread to the lungs and bone. Although it was previously believed that some cases of GIST are benign (do not spread), it is now understood that all GISTs have some potential to metastasize, with risk ranging from very low to high. A better understanding of GIST biology has also revealed that its prevalence varies across racial and ethnic groups.

Most GISTs result from a non-inherited change (mutation) in one of two genes, KIT or PDGFRA, which leads to inappropriate and ongoing division of tumor cells. However, approximately 10%–15% of cases of GIST in adults and 85% of cases in children are not associated with mutations in either the KIT or PDGFRA genes. These previously uncategorized cases were originally grouped under the umbrella terms “wild-type GIST” and “pediatric-like GIST.” Advances in research have since revealed that these tumors have mutations in as many as 20 other genes, and defining the specific mutations in individual patients can help guide further research and treatment.

Most GIST-causing mutations arise randomly and are not inherited. However, there are rare cases in which a gene mutation is inherited, for example in succinate dehydrogenase (SDH)-deficient GIST associated with Carney–Stratakis syndrome (CSS; also known as GIST-paraganglioma syndrome). Though most GIST arise in older adults, these rarer cases of inherited GIST often present in children, adolescents, and young adults.

GIST is most commonly diagnosed by pathological analysis of biopsy tissue taken during an endoscopy or through the skin. Computed tomography (CT) and magnetic resonance (MR) imaging are also used to diagnose GIST and determine the location and extent of the tumor. Molecular characterization of the tumor, through identification of specific gene mutations or the presence of markers on the tumor surface, provides further information for diagnosis and can help guide treatment.

Surgical removal is the most common treatment for GIST that has not spread, and an operation provides the best chance of a cure if the tumor is completely removed. In cases where the tumor has spread, oral chemotherapy (i.e., pills) is usually indicated in conjunction with surgery. The most frequently used drugs are tyrosine kinase inhibitors (e.g., Gleevec), which target the commonly observed mutations in KIT and PDFGRA. Patients respond differently to the range of available tyrosine kinase inhibitors, so it can be useful to test for specific mutations in the tumor when selecting a course of therapy. Clinical trials are also underway to target subtypes of GIST with rare genetic abnormalities. Finally, it is noteworthy that there is no role for radiation therapy in the management of GIST.